Title:Cancer Resistance to Type II Topoisomerase Inhibitors
VOLUME: 19 ISSUE: 23
Author(s):P. Pilati, D. Nitti and S. Mocellin
Affiliation:Department of Oncological and Surgical Sciences, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
Keywords:Cancer, chemoresistance, chemotherapy, topoisomerase, DNA repair, Type II topoisomerases, ubiquitously expressed enzymes, genomic DNA, drugs, biology of TOPO2 inhibitors
Abstract:Type II topoisomerases (TOPO2) are ubiquitously expressed enzymes that overcome topological problems in genomic DNA,
which can result from DNA replication, transcription and repair. The class of compounds targeting TOPO2 includes some of the most
active chemotherapy agents currently available for the treatment of patients with different cancer types. Therefore, understanding of the
molecular mechanisms underlying resistance to these drugs is of pivotal importance to improve their efficacy and ultimately increase the
life expectancy of cancer patients. The first aim of this review is to summarize the molecular biology of TOPO2 inhibitors, which is the
key to understand cancer resistance to them; the second part of this work is dedicated to overview and discuss the available evidence on
the mechanisms of resistance to these drugs, with special attention to the strategies that might be useful to circumvent this phenomenon
on the clinical ground.
